Aims: The organic anion transporter polypeptide 2B1 (OATP2B1) is a membrane transporter known to carry a variety of endogeneous compounds and drugs. To date, there is a lack of knowledge on its pharmacological and physiological role. However studies suggest an impact on metabolism including steroid hormones. Our study aimed to investigate the function of OATP2B1 in glucose homeostasis and and phenotypical development. Methods: Approximately 3-month-old female and male rats of different genotypes for OATP2B1 (humanized knockin, whole-body absence knockout rats and, as a reference, the ordinatory wildtype rat) were analyzed for weight and surface area. Additionally, energy expenditure was determined and the impact on glucose homeostasis by intraperitoneal glucose and insulin injection assessed. The impact on long term development was implemented by a comparison of differences in body weight and surface area and furthermore in organ weight and surface area in 6- and 12-month-old knockout and ordinary wildtype animals.
Results: Knockout animals showed a lower energy expenditure and a negative influence on glucose break down. Moreover, phenotypical analysis suggested a long term effect of Slco2b1 knockout with regard to organ size and/or weight especially in the brain, pancreas, kidneys, spleen and possibly colon in male and/or female with an overall tendency to develop obesity. Humanized animals exhibited a lower food intake and weight development in general, but no clearly defined impact on glucose secretion. A reduction in brain tissue in female was observed in general as well.
Conclusion: Our study led to the assumption that OATP2B1 has an influence on glucose homeostasis and may have an influence on phenotypical development at each age and in each gender, but the exact explanation for its various distributions and appearance is not clear yet.